Ethanolic Ginkgo biloba leaf extract prevents renal fibrosis through Akt/mTOR signaling in diabetic nephropathy

Lü, Qian; Zuo, Wen-Zi; Ji, Xiaojun; Zhou, Yuexian; Liu, Yuqing; Yao, Xiaoqin; Zhou, Xueyan; Liu, Yao-Wu; Zhang, Fan; Yin, Xiaoxing

doi:10.1016/j.phymed.2015.08.010

Cited by 69 publications

(36 citation statements)

References 30 publications

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“…The phosphorylation of AKT and mTOR is a landmark reaction of DN [41]. Akt/mTOR pathway is a potential target to prevent renal fibrosis in DN [42]. MiR-196b and miR-451 influence the cell proliferation and invasion through regulating PI3K/AKT/mTOR pathway in cancer cells [43,44].…”

Section: Discussionmentioning

confidence: 99%

Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

Zhao

Jin

et al. 2020

Bioscience Reports

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Objective: The present study aimed to investigate the regulatory role of long non-coding RNA plasmacytoma variant translocation 1 (PVT1) on high glucose (HG)-induced mouse mesangial cells (MMCs). Methods: PVT1 expression in diabetic nephropathy (DN) mice and HG-induced MMCs was detected by qRT-PCR. EdU and Colony formation, Annexin V-PI staining, Muse cell cycle, Scratch, and Transwell assays were performed to detect the cell proliferation, apoptosis, cell cycle, migration, and invasion, respectively. The contents of fibrosis factors in cell-culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to detect the expression of factors involved in apoptosis, cell cycle, migration and invasion, fibrosis, and PI3K/Akt/mTOR pathway. The targeting relation between miR-93-5p and PVT1 was predicted by StarBase3.0 (an online software for analyzing the targeting relationship) and identified by Dual-luciferase reporter (DLR) assay. Results: PVT1 was overexpressed in DN kidney tissues and HG-induced MMCs. HG-induced MMCs exhibited significantly increased EdU-positive cells, cell colonies, S and G2/M phase cells, migration and invasion ability, and contents of fibrosis factors, as well as significantly decreased apoptosis rate compared with NG-induced MMCs. HG significantly up-regulated Bcl-2, CyclinD1, CDK4, N-cadherin, vimentin, Col. IV, FN, TGF-β1 and PAI-1, and down-regulated Bax, cleaved caspase-3, cleaved PARP, and E-cadherin in MMCs. Silencing of PVT1 eliminated the effects of HG in MMCs and blocked PI3K/Akt/mTOR pathway. MiR-93-5p was a target of PVT1, which eliminated the effects of PVT1 on HG-induced MMCs. Conclusions: PVT1 silencing inhibited the proliferation, migration, invasion and fibrosis, promoted the apoptosis, and blocked PI3K/Akt/mTOR pathway in HG-induced MMCs via up-regulating miR-93-5p.

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Section: Discussionmentioning

confidence: 99%

Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

Zhao

Jin

et al. 2020

Bioscience Reports

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“…14,15) In addition to improving renal fibrosis, BMP-7 treatment attenuated EMT process of renal tubular epithelial cells induced by TGF-β1 and reduced ECM production in mesangial cells. [16][17][18] Our previous study has shown that Ginkgo biloba extract (GbE) attenuated RIF caused by diabetes. GbE is a multicomponent mixture contains flavonoids and terpene lactones.…”

Section: Introductionmentioning

confidence: 99%

“…The flavonoids that have been identified mainly include rutin, myricetin, quercetin, luteolin, kaempferol, isorhamnetin and genistein. 19) Among the flavonoid components, the effects of rutin, quercetin and myricetin have been reported in renal fibrosis induced by diabetes and UUO and in EMT process of renal tubular epithelial cells. [20][21][22][23] However, the effects of luteolin, kaempferol, isorhamnetin and genistein on RIF are rarely studied.…”

Section: Introductionmentioning

confidence: 99%

Kaempferol Protects Renal Fibrosis through Activating the BMP-7-Smad1/5 Signaling Pathway

Cao

Zhang

et al. 2020

Biological & Pharmaceutical Bulletin

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Renal interstitial fibrosis (RIF) is a common pathological characteristic associated with end-stage renal disease. However, treatment strategies for RIF are still very limited. In this study, we reported that kaempferol, a classic flavonoid, exhibited strong and widely inhibitory effect on the expression of fibrosis related genes in transforming growth factor beta 1 (TGF-β1) treated NRK-52E cells. Further studies revealed that kaempferol inhibited TGF-β1 induced epithelial-mesenchymal transition (EMT) process of NRK-52E cells and improved renal function deterioration and RIF in unilateral ureteral obstruction (UUO) rats. After exploring the underlying mechanisms, we found that kaempferol was able to activate the BMP-7-Smad1/5 pathway, rather than the TGF-β1-Smad2/3 pathway. To further validate these results, DMH1 and BMP-7 knockdown were utilized at the cellular level and the results showed that both methods were able to antagonize the effects of kaempferol on the EMT process of NRK-52E cells induced by TGF-β1. In UUO rats, inhibition of BMP-7 signaling by DMH1 also reversed the effects of kaempferol on renal function decline and RIF. Taken together, our findings demonstrated that kaempferol could be a good candidate for renal fibrosis treatment.

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“…The phosphorylation of AKT and mTOR is a landmark reaction of DN [43]. Akt/mTOR pathway is a potential target to prevent renal fibrosis in DN [44]. MiR-196b and miR-451 influence the cell proliferation and invasion through regulating PI3K/AKT/mTOR pathway in cancer cells [45,46].…”

Section: Discussionmentioning

confidence: 99%

Silencing of Long non-coding RNA Plasmacytoma variant translocation 1 inhibits the proliferation, migration, invasion and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

Zhao

Jin

et al. 2019

Preprint

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Background: This study aimed to investigate the regulatory role of Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) on the biological processes of high glucose (HG)-induced mouse mesangial cells (MMCs). Methods: PVT1 expression in diabetic nephropathy (DN) mice and HG-induced MMCs was detected by qRT-PCR. PVT1 was silenced in HG-induced MMCs by the transfection of PVT1 siRNA (si-PVT1). EdU and Colony formation, Annexin V-PI staining, Muse cell cycle, Scratch, and Transwell assay were performed to detect the cell proliferation, apoptosis, cell cycle, migration, and invasion, respectively. The contents of fibrosis factors in cell-culture supernatants were detected by ELISA. Western blot was performed to detect the expression of factors involved in apoptosis, cell cycle, migration and invasion, fibrosis, and PI3K/Akt/mTOR pathway. In addition, the targeting relation between miR-93-5p and PVT1 was predicted by StarBase3.0 and identified by Dual-luciferase reporter gene assay. Results: PVT1 was overexpressed in DN kidney tissues and HG-induced MMCs. HG-induced MMCs exhibited significantly increased EdU positive cells, cell colonies, S and G2/M phase cells, migration and invasion ability, and contents of fibrosis factors, as well as significantly decreased apoptosis rate compared with NG-induced MMCs. HG significantly up-regulated Bcl-2, CyclinD1, CDK4, N-cadherin, vimentin, Col. IV, FN, TGF-β1 and PAI-1, and down-regulated Bax, cleaved caspase-3, cleaved PARP, and E-cadherin in MMCs. Silencing of PVT1 eliminated the effects of HG in MMCs and blocked PI3K/Akt/mTOR pathway. MiR-93-5p was a target of PVT1, which eliminated the effects of PVT1 on HG-induced MMCs. Conclusions: PVT1 silencing inhibited the proliferation, migration, invasion and fibrosis, promoted the apoptosis, and blocked PI3K/Akt/mTOR pathway in HG-induced MMCs via up-regulating miR-93-5p.

show abstract

Ethanolic Ginkgo biloba leaf extract prevents renal fibrosis through Akt/mTOR signaling in diabetic nephropathy

Cited by 69 publications

References 30 publications

Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

Kaempferol Protects Renal Fibrosis through Activating the BMP-7-Smad1/5 Signaling Pathway

Silencing of Long non-coding RNA Plasmacytoma variant translocation 1 inhibits the proliferation, migration, invasion and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

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